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J Neurosurg Anesthesiol. 2013 Jul;25(3):306-10. doi: 10.1097/ANA.0b013e318283c3c7.

Biphasic change of progenitor proliferation in dentate gyrus after single dose of isoflurane in young adult rats.

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  • 1Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143-0542, USA.



Isoflurane exposure causes improvement in long-term neurocognitive function in young adult rats; this is associated with an increase in dentate gyrus (DG) progenitor proliferation 4 days after anesthesia. However, the number of new neurons that were born from cells that incorporated bromodeoxyuridine (BrdU) 4 days after anesthesia is not affected by anesthesia. We tested the hypothesis that progenitor proliferation continues to increase past 4 days, which would imply the possibility that the number of new neurons after anesthesia could be increased if BrdU labeling occurred at a later time point.


BrdU was injected at 0, 1, 2, 4, 9, 16 days after 4 hours of isoflurane exposure to 60-day old rats. Brains were harvested 2 hours later, immunohistochemically stained, and the number of BrdU+ cells in the DG was assessed microscopically.


After 4 hours of exposure to isoflurane in 60-day old rats, the number of BrdU+ cells decreased on days 0 to 2, then increased on day 4 significantly, and regressed toward the control level on days 9 and 16.


Anesthesia-induced progenitor proliferation in the DG was not sustained 9 days after anesthesia. We interpret these results to signify that an anesthetic effect on neurogenesis likely does not play a critical role in the previously observed isoflurane-induced long-term improvement in neurocognitive function in 60-day old rats and that the transient increase in progenitor proliferation serves to replenish the pool of neural stem cells. The mechanism of anesthesia-induced improvement in cognition of young adult rats remains elusive.

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